Experiments designed to obtain detailed understanding of neurotransmitter hormone and drug actions involving cyclic nucleotides in the nervous system are planned. A specific protein calcium-dependent regulator of adenylate cyclase will be examined further in glial tumor cells and in primary glial cultures for its role in coupling of norepinephrine action to cyclic AMP and Ca2-ion functions. Alterations in phosphorylation of proteins endogenous to C-6 glial tumor cells will be studied in relationship to the cyclic GMP content of cells. The role of cyclic GMP in gene expression, particularly in the heat shock phenomenon exhibited by Drosophila cells and by fibroblasts, will be examined in view of its possible relevance to certain human neurological diseases.